Adoptive Cell Transfer Combined With Peptide Vaccination in Transiently Immunosuppressed Melanoma Patients

Phase I Study of in Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma

Patients with advanced stage melanoma who underwent vaccination with the Melan-A/MART-1 peptide and who display detectable levels of Melan-A specific CD8+ T cells in peripheral blood are eligible for this trial. After collecting and freezing of these tumor specific T cells via apheresis, patients undergo a single cycle of immunosuppressive chemotherapy. 3 days after, cells are reinfused and peptide vaccination continued. The aim of this immunotherapy protocol is to boost tumor specific T cells during the immune recovery period in order to reinforce the patients' immune response against the tumor.

Study Overview

• Status: Suspended
• Conditions: Melanoma
• Intervention / Treatment: Biological: Melan-A analog peptide

Detailed Description

Patients who have previously been vaccinated with Melan-A/MART-1 peptide are eligible. Whole PBMC's containing Melan-A specific CD8+ lymphocytes are collected via lymphocytapheresis and freezed. Lymphodepleting chemotherapy consists of 2 days of Busulfan 2mg/kg at days -7,-6, followed by Fludarabine 30mg/m2 at days -5,-4,-3. At day 0, whole untreated PBMC's are reinfused to the patient and vaccination with Melan-A analog peptide is restarted and repeated every 4 weeks. Immunomonitoring with detailed FACS analysis using tetramers is performed at day 0,8,15,30, and then monthly. The aim is to boost Melan-A specific CD8 T cells in vivo during homeostatic proliferation after lymphodepletion and antigen driven proliferation due to peptide vaccination.

• Study Type: Interventional
• Enrollment: 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1011
    • Multidisciplinary Oncology Center, University of Lausanne Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage IV melanoma
• tumor expressing Melan-A
• patient of HLA-A2 subtype
• Detectable immune response after peptide vaccination with Melan-A
• Disease progression during peptide vaccination

Exclusion Criteria:

• Cerebral metastases
• rapidly progressive disease, that necessitates systemic chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity and feasibility

Secondary Outcome Measures

Outcome Measure
Immunomonitoring of the immune reconstitution period

Collaborators and Investigators

• Sponsor: University of Lausanne Hospitals
• Collaborators: Fond'action contre le cancer; Barletta Foundation; NCCR (National Center of Competence in Resaerch, Switzerland)
• Investigators: Principal Investigator: Verena Voelter, MD, Multidisciplinary Oncology Center, University of Lausanne Hospitals

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Study Completion: August 1, 2005

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (ESTIMATE): September 12, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): September 12, 2005
• Last Update Submitted That Met QC Criteria: September 8, 2005
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: melanoma; Adoptive cell transfer; peptide vaccination; immunosuppression and homeostatic proliferation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: CePO-ITA-01